We found that Sirt6loxp/loxp;Cre− mice had significantly higher levels of secreted TNFα in the peritoneal cavity than Sirt6loxp/loxp;Cre + mice (Fig. 7H), confirming that SIRT6 deletion in macrophages ameliorates TNFα secretion in vivo during obesity. Here, SIRT6 is linked to obesity due to melanocortin 4 receptor deficiency.